A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer

Ovarian Cancer Clinical Trial

— FORWARD I  

Official title:

FORWARD I: A Randomized, Open Label Phase 3 Study to Evaluate the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) Versus Investigator's Choice of Chemotherapy in Women With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02631876
• Other study ID #: IMGN853-0403
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2016
• Est. completion date: January 2020

Study information

• Verified date: September 2020
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of mirvetuximab soravtansine to that of selected single-agent chemotherapy (Investigator's choice) in women with platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian tube cancer.

Description:

Participants will be randomized to either mirvetuximab soravtansine or investigator's choice chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 366
• Est. completion date: January 2020
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must be diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer

• Participants must have folate receptor alpha positive tumor expression as defined in the protocol

• Participants must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy.

• Participants must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment

• Participants must have at least one lesion that meets the definition of measurable disease by RECIST 1.1

Exclusion Criteria:

• Diagnosis of clear cell, low grade ovarian cancer or mixed tumors

• Participants with primary platinum-refractory disease

• Serious concurrent illness or clinically relevant active infection as defined in the protocol

• Prior treatment with mirvetuximab soravtansine

• Women who are pregnant or breast feeding

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Primary Peritoneal Carcinoma

Intervention

Drug:
• Mirvetuximab soravtansine
Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm.
• Paclitaxel
Paclitaxel will be administered per dose and schedule specified in the arm.
• Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.
• Topotecan
Topotecan will be administered per dose and schedule specified in the arm.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	AZ Groeninge - Oncology Centre	Kortrijk
Belgium	Universitaire Ziekenhuizen (UZ) Leuven-Gasthuisberg	Leuven
Belgium	Centre Hospitalier de l'Ardenne	Libramont
Bosnia and Herzegovina	University Clinical Center of Republic of Srpska	Banja Luka
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Hopital de la CitedelaSante	Laval	Quebec
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre hospitalier de l'Université de Montréal	Montreal	Quebec
Canada	McGill University Health Centre - Glen Site	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute - Odette Cancer Centre	Toronto	Ontario
Czechia	Porodnicka A Gynekologicka Klinika	Hradec Králové
Czechia	University Hospital Ostrava	Ostrava Poruba
Czechia	Onkologicke oddeleni Krajske nemocnice T. Bati, a.s., Zlin	Zlín
France	Institut de Cancerologie de L'Ouest - site Paul Papin	Angers
France	CHRU Jean Minjoz	Besançon
France	Institut Bergonie	Bordeaux
France	Cochin Hospital	Paris
France	Hôpital Croix St-Simon	Paris
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	Centre Armoricain de radiotherapie, Imagerie Medicale et Oncol	Plérin
France	Centre Eugene Marquis	Rennes
France	Institut Curie-Hopital Rene Huguenin	Saint-Cloud
France	Institut Claudius Regaud	Toulouse
France	Institut de Cancerologie de Lorraine	Vandœuvre-lès-Nancy
France	Gustave Roussy Institution	Villejuif
Ireland	Bon Secours Hospital	Cork
Ireland	Mater Private Hospital and Mater Misericordiae University Hospital	Dublin
Italy	Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna
Italy	Azienda Sanitaria Locale (ASL)	Brindisi
Italy	Azienda Unita Sanitaria Locale di Ravenna	Faenza
Italy	Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica	Meldola (FC)
Italy	Fondazione IRCCS National Cancer Institute	Milan
Italy	Ospedale San Raffaele	Milan
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Istituto Nazionale Tumori- G. Pascale	Naples
Italy	Policlinico Universitario Agostino Gemelli	Roma
Russian Federation	LLC "VitaMed"	Moscow
Russian Federation	State Budget-Funded Healthcare Institution of Novosibirsk Oblast "Novosibirsk Oblast Oncology Dispensary"	Novosibirsk
Russian Federation	Budget-Funded Healthcare Institution of Omsk Oblast "Clinical Oncology Dispensary"	Omsk
Russian Federation	State Budget Institution of Health "Leningrad Regional Oncologicacal Dispensary"	Saint Petersburg
Serbia	Oncology and Radiology Institute Serbia	Belgrade
Serbia	Clinical Centre Nis, Oncology Clinic	Niš
Serbia	Oncology Institute Vojvodina	Sremska Kamenica
Spain	Hospital Teresa Herrera (CHUACoruña)	A Coruña
Spain	ICO Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Institut Català d'Oncologia - Unitad de Investigación Clínica	Barcelona
Spain	IOR - Hospital Quiron Dexeus	Barcelona
Spain	Hospital Reina Sofia	Córdoba
Spain	Onkologikoa	Donostia San Sebastian	Gipuzkoa
Spain	Complejo Hospitalario Granada	Granada
Spain	Hospital Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	MD Anderson Cancer Center - Madrid	Madrid
Spain	Servicio de Oncología Médica Hospital Universitario La Paz	Madrid
Spain	Hospital Regional Universitario Malaga - Hospital Materno Infantil de Málaga	Malaga
Spain	Hospital Son Llatzer (HSLL)	Palma de Mallorca
Spain	Instituto Valenciano de Oncologia	Valencia
Switzerland	Hopitaux Universitaires de Geneve	Geneve
Switzerland	Kantonsspital	Winterthur	Zurich
Switzerland	Kantonsspital Winterthur, Medizinische Onkologie	Winterthur	Zurich
United Kingdom	University Hospitals Coventry & Warwickshire NHS Trust, Arden Cancer Centre	Coventry
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	Nottingham University Hospitals NHS Trust - City Hospital	Nottingham	England
United Kingdom	Peterborough City Hospital	Peterborough	Great Britain
United Kingdom	Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital	Preston	England
United Kingdom	Cancer,Haematology and Physics Directorate, Cancer Centre Royal Stoke University	Stoke-on-Trent	Staffordshire
United Kingdom	The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH)	Sutton	England
United Kingdom	The Royal Wolverhampton Hospitals NHS Trust - New Cross Hospital - GOW	Wolverhampton	England
United States	The University of New Mexico Comprehensive Cancer Center - Memorial Medical Center	Albuquerque	New Mexico
United States	Georgia Regents University (GRU)-Medical College of Georgia (MCG) - Cancer Center	Augusta	Georgia
United States	Texas Oncology-Austin Central	Austin	Texas
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	MD Anderson Cancer Center - Cooper Health	Camden	New Jersey
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Levine Cancer Institute - Carolinas Medical Center	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Fairview Hospital, Moll Pavilion Cancer Center	Cleveland	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Women's Cancer Care	Covington	Louisiana
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Texas Oncology - Fort Worth	Fort Worth	Texas
United States	Sudarshan Sharma LTD	Hinsdale	Illinois
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Kadlec Clinic Hematology & Oncology	Kennewick	Washington
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA Women's Health Clinical Research Unit - OBGYN	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Hillcrest Hospital	Mayfield	Ohio
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center and (MSK Monmouth) and ( MSK Westchester)	New York	New York
United States	Norwalk Hospital/WCHN	Norwalk	Connecticut
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Magee - Womens Hospital of UPMC	Pittsburgh	Pennsylvania
United States	Women & Infants of Rhode Island	Providence	Rhode Island
United States	Center of Hope	Reno	Nevada
United States	University of California San Diego Medical Center	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	Florida State University College of Medicine	Sarasota	Florida
United States	WK Physician Network Clinical Research	Shreveport	Louisiana
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Mercy Women's Oncology	Springfield	Missouri
United States	Overlook Medical Center	Summit	New Jersey
United States	Arizona Oncology Associates, PC - HAL	Tempe	Arizona
United States	Texas Oncology - The Woodlands, Gynecologic Oncology	The Woodlands	Texas
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute, LLC	Tulsa	Oklahoma
United States	Texas Oncology-Tyler	Tyler	Texas
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
ImmunoGen, Inc.	Gynecologic Oncology Group

Countries where clinical trial is conducted

United States,  Belgium,  Bosnia and Herzegovina,  Canada,  Czechia,  France,  Ireland,  Italy,  Russian Federation,  Serbia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study	PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (SoD) of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Primary	PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (= 75% of Tumor Staining)	PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1	ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the SoD of target lesions, taking as reference the baseline SoD.	From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Overall Survival (OS)	OS was defined as the time from the date of randomization until the date of death from any cause. Participants who did not experience the event of death were censored at their last date known to be alive. OS was estimated using the Kaplan-Meier method.	From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Number of Participants Achieving at Least a 15% (= 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28-item ovarian cancer supplemental module. It comprises of 6 symptom scales (AB/GI symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease, treatment), and sexual functioning. Participants were asked to indicate extent to which they experienced AB/GI symptoms. Participants responded on a scale of 1-4(1=not at all, 2=a little, 3=quite a bit, 4=very much) to following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data were transformed to a scale from 0-100. Lower scores=better health.	Baseline, Week 8/9
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Adverse event (AE): any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. Severity: graded per National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Relation of AE to treatment was determined by investigator. Serious AEs: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent/significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: any AE that emerged on or after the first dose, and within 30 days of the last dose. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported AEs module.	From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses	CA-125 Response rate wasdefined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100.	From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	PFS, as Assessed by Investigator Per RECIST Version 1.1	PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.	From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1	DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of PD. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier.	From the date of first response (CR or PR) until the date of PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary	Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4	PK parameters were calculated using standard non-compartmental methods.	Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3
Secondary	Number of Participants With Anti-Drug Antibodies (ADA)	An electrochemiluminescent method was used for the detection of anti-mirvetuximab soravtansine antibodies in plasma from samples collected in dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The qualitative assay was designed to detect anti-mirvetuximab soravtansine antibodies in human plasma.	Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6